托法替布是一种口服 Janus 激酶抑制剂，用于治疗溃疡性结肠炎 (UC)。我们报告了已完成的全球 UC 临床计划中托法替布安全性的综合总结（托法替布最大暴露量为 9.2 年）。该分析包括来自已完成的 2/3 期安慰剂对照研究的接受托法替布 5 或 10 毫克每日两次（每日两次）的患者，开放标签、长期延伸研究和随机 3b/4 期研究。对死亡和特别关注的不良事件 (AESI) 的比例和发生率（IR；发生事件的独特患者/100 患者年 [PY] 暴露）进行了评估。总体而言，1157 名患者接受了≥1 剂托法替布 5或 10 毫克，每日两次； 938 例 (81.1%) 服用托法替布 10 mg b.i.d. 的主要剂量。团体; 552 人 (47.7%) 接受托法替布治疗≥2 年；总暴露量：3202.0 PY； 994 (85.9%) 名经历过 AE； 254 名 (22.0%) 经历了严重的 AE。中位治疗持续时间：1.7（范围 0.0-9.2）年。联合托法替布剂量的 IR (95% CI)：死亡 0.24 (0.10-0.48)；严重感染（SI）1.80（1.37-2.32）；带状疱疹（HZ；非严重和严重）3.24（2.63-3.94）；严重HZ 0.24（0.10-0.48）；机会性感染0.96（0.65-1.36）；恶性肿瘤（不包括非黑色素瘤皮肤癌 [NMSC]）0.88 (0.59-1.26)； NMSC 0.71（0.45-1.07）；主要不良心血管事件0.27（0.12-0.52）；深静脉血栓0.06（0.01-0.22）；肺栓塞0.18（0.07-0.40）；胃肠道穿孔 0.09 (0.02-0.27)。除 HZ 和 SI 外，AESI 的 IR 均<1 例/100 PY。安全性与之前对较短暴露时间的分析以及托法替布的已知安全性特征（包括真实世界数据）一致。GOV：NCT00787202； NCT01465763； NCT01458951； NCT01458574； NCT01470612； NCT03281304.© 2024 辉瑞公司和作者。 《联合欧洲胃肠病学杂志》由 Wiley periodicals LLC 代表联合欧洲胃肠病学出版。

Tofacitinib is an oral Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We report an integrated summary of tofacitinib safety from the completed global UC clinical program (9.2 years maximum tofacitinib exposure).This analysis included patients receiving tofacitinib 5 or 10 mg twice daily (b.i.d.) from completed phase 2/3 placebo-controlled studies, an open-label, long-term extension study and a randomized phase 3b/4 study. Proportions and incidence rates (IRs; unique patients with events/100 patient-years [PY] of exposure) were evaluated for deaths and adverse events (AEs) of special interest (AESI).Overall, 1157 patients received ≥1 dose of tofacitinib 5 or 10 mg b.i.d.; 938 (81.1%) were in the predominant dose tofacitinib 10 mg b.i.d. group; 552 (47.7%) received tofacitinib for ≥2 years; total exposure: 3202.0 PY; 994 (85.9%) experienced AEs; 254 (22.0%) experienced serious AEs. Median treatment duration: 1.7 (range 0.0-9.2) years. IRs (95% CI) for combined tofacitinib doses: deaths 0.24 (0.10-0.48); serious infections (SIs) 1.80 (1.37-2.32); herpes zoster (HZ; non-serious and serious) 3.24 (2.63-3.94); serious HZ 0.24 (0.10-0.48); opportunistic infections 0.96 (0.65-1.36); malignancies (excluding non-melanoma skin cancer [NMSC]) 0.88 (0.59-1.26); NMSC 0.71 (0.45-1.07); major adverse cardiovascular events 0.27 (0.12-0.52); deep vein thrombosis 0.06 (0.01-0.22); pulmonary embolism 0.18 (0.07-0.40); and gastrointestinal perforations 0.09 (0.02-0.27).Except for HZ and SIs, IRs for AESI were <1 case/100 PY. Safety was consistent with previous analyses of shorter exposure and tofacitinib's known safety profile, including real-world data.GOV: NCT00787202; NCT01465763; NCT01458951; NCT01458574; NCT01470612; NCT03281304.© 2024 Pfizer Inc. and The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.